Cancer of the Gallbladder and Biliary Tree

  • Marco Filauro
  • Giulio Angelini
  • Federico Fazio
  • Andrea Barberis


Cholangiocarcinoma and gallbladder carcinoma are uncommon and aggressive cancers of the biliary system; its incidence is rising worldwide, and it has a poor prognosis given that the diagnosis is often delayed due to subtle symptoms. Radical surgical resection is the only possible curative treatment, but only few patients are resectable at the time of the diagnosis. Surgical procedures are different according to tumor location and, in some cases, need highly demolitive interventions. Alternative palliative procedures are available as well as systematic chemo- and radiotherapy that need to be organized within a multidisciplinary team, ideally in a high-volume center. In this chapter, we illustrate the various aspects in which this disease presents and possible therapeutic and palliative options, with an eye to the elderly population that almost exclusively characterizes patients with which we deal every day in our clinical practice. Although until a few years ago old age was considered a contraindication to surgery, ever more studies are showing how age per se is not a contraindication to surgery.


Gallbladder cancer Biliary tree cancer Cholangiocarcinoma Intrahepatic Perihilar Obstructive jaundice Liver surgery Pancreaticoduodenectomy 


  1. 1.
    Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006;118:1591–602. Scholar
  2. 2.
    Lazcano-Ponce EC, Miquel JF, Muñoz N, Herrero R, Ferrecio C, Alonso de Ruiz P, et al. Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin. 2001;51:349–64.CrossRefGoogle Scholar
  3. 3.
    Xu HL, Cheng JR, Andreotti G, Gao YT, Rashid A. Cholesterol metabolism gene polymorphisms and the risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China. Carcinogenesis. 2011;32:58–62. Scholar
  4. 4.
    Sheth S, Bedford A, Chopra S. Primary gallbladder cancer: recognition of risk factors and the role of prophylactic cholecystectomy. Am J Gastroenterol. 2000;95:1402–10. Scholar
  5. 5.
    Shimizu M, Miura J, Tanaka T, Itoh H, Saitoh Y. Porcelain gallbladder. Relation between its type by ultrasound and incidence of cancer. J Clin Gastroenterol. 1989;11:471–6.CrossRefGoogle Scholar
  6. 6.
    Babu BI, Dennison AR, Garcea G. Management and diagnosis of gallbladder polyps: a systematic review. Langenbeck’s Arch Surg. 2015;400:455–62. Scholar
  7. 7.
    Duffy A, Capanu M, Abou-Alfa GK, Huitzil D, Jarnagin W, Fong Y, et al. Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol. 2008;98:485–9. Scholar
  8. 8.
    Boerma EJ. Towards an oncological resection of gall bladder cancer. Eur J Surg Oncol. 1994;20:537–44.PubMedGoogle Scholar
  9. 9.
    Jin K, Lan H, Zhu T, He K, Teng L. Gallbladder carcinoma incidentally encountered during laparoscopic cholecystectomy: how to deal with it. Clin Transl Oncol. 2011;13:25–33. Scholar
  10. 10.
    Miller G, Jarnagin WR. Gallbladder carcinoma. Eur J Surg Oncol. 2008;34:306–12. Scholar
  11. 11.
    Konstantinidis IT, Deshpande V, Genevay M, Berger D, Fernandez-del Castillo C, Tanabe KK, Zheng H, et al. Trends in presentation and survival for gallbladder cancer during a period of more than 4 decades: a single-institution experience. Arch Surg. 2009;144:441–7. Scholar
  12. 12.
    Yamaguchi K, Chijiiwa K, Ichimiya H, Sada M, Kawakami K, Nishikata F, et al. Gallbladder carcinoma in the era of laparoscopic cholecystectomy. Arch Surg. 1996;131:981–4.CrossRefGoogle Scholar
  13. 13.
    A prospective analysis of 1518 laparoscopic cholecystectomies. The Southern Surgeons Club. N Engl J Med. 1991;324:1073–8.
  14. 14.
    Kanthan R, Senger JL, Ahmed S, Kanthan SC. Gallbladder cancer in the 21st century. J Oncol. 2015;2015:967472. Scholar
  15. 15.
    National Comprehensive Cancer Network. Hepatobiliary Cancer (Version 2.2016). Accessed December 20, 2016.
  16. 16.
    Agarwal AK, Kalayarasan R, Javed A, Gupta N, Nag HH. The role of staging laparoscopy in primary gall bladder cancer—an analysis of 409 patients: a prospective study to evaluate the role of staging laparoscopy in the management of gallbladder cancer. Ann Surg. 2013;258:318–23. Scholar
  17. 17.
    Maker AV, Butte JM, Oxenberg J, Kuk D, Gonen M, Fong Y, et al. Is port site resection necessary in the surgical management of gallbladder cancer? Ann Surg Oncol. 2012;19:409–17. Scholar
  18. 18.
    Soupault R, Couinaud C. New procedure for intrahepatic biliary shunt: left cholangiojejunostomy without hepatic sacrifice. Presse Med. 1957;65:1157–9.PubMedGoogle Scholar
  19. 19.
    Renshaw K. Malignant neoplasms of the extrahepatic biliary ducts. Ann Surg. 1922;76:205–21.CrossRefGoogle Scholar
  20. 20.
    Pitt HA, Dooley WC, Yeo CJ, Cameron JL. Malignancies of the biliary tree. Curr Probl Surg. 1995;32:1–90.CrossRefGoogle Scholar
  21. 21.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30. Scholar
  22. 22.
    Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004;24:115–25. Scholar
  23. 23.
    Broomé U, Olsson R, Lööf L, Bodemar G, Hultcrantz R, Danielsson A, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38:610–5.CrossRefGoogle Scholar
  24. 24.
    Kubo S, Kinoshita H, Hirohashi K, Hamba H. Hepatolithiasis associated with cholangiocarcinoma. World J Surg. 1995;19:637–41.CrossRefGoogle Scholar
  25. 25.
    Hardell L, Bengtsson NO, Jonsson U, Eriksson S, Larsson LG. Aetiological aspects on primary liver cancer with special regard to alcohol, organic solvents and acute intermittent porphyria—an epidemiological investigation. Br J Cancer. 1984;50:389–97.CrossRefGoogle Scholar
  26. 26.
    Sahani D, Prasad SR, Tannabe KK, Hahn PF, Mueller PR, Saini S. Thorotrast-induced cholangiocarcinoma: case report. Abdom Imaging. 2003;28:72–4. Scholar
  27. 27.
    Sorensen HT, Friis S, Olsen JH, Thulstrup AM, Mellemkjaer L, Linet M, et al. Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark. Hepatology. 1998;28:921–5. Scholar
  28. 28.
    Shin HR, Lee CU, Park HJ, Seol SY, Chung JM, Choi HC, et al. Hepatitis B and C virus, Clonorchis Sinensis for the risk of liver cancer: a case-control study in Pusan, Korea. Int J Epidemiol. 1996;25:933–40.CrossRefGoogle Scholar
  29. 29.
    Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, et al. Incidence of primary cholangiocellular carcinoma of the liver in japanese patients with hepatitis C virus-related cirrhosis. Cancer. 2000;88:2471–7.CrossRefGoogle Scholar
  30. 30.
    Watanapa P, Watanapa WB. Liver fluke-associated cholangiocarcinoma. Br J Surg. 2002;89:962–70. Scholar
  31. 31.
    Rustagi T, Dasanu CA. Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates. J Gastrointest Cancer. 2012;43:137–47. Scholar
  32. 32.
    Ohtsuka T, Inoue K, Ohuchida J, Nabae T, Takahata S, Niiyama H, et al. Carcinoma arising in choledochocele. Endoscopy. 2001;33:614–9. Scholar
  33. 33.
    DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg. 2007;245:755–62. Scholar
  34. 34.
    Bismuth H, Nakache R, Diamond T. Management strategies in resection for hilar cholangiocarcinoma. Ann Surg. 1992;215:31–8.CrossRefGoogle Scholar
  35. 35.
    Blechacz B, Komuta M, Roskams T, Gores GJ. Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 2011;8:512–22. Scholar
  36. 36.
    Mann DV, Edwards R, Ho S, Lau WY, Glazer G. Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol. 2000;26:474–9. Scholar
  37. 37.
    Saini S. Imaging of the hepatobiliary tract. N Engl J Med. 1997;336:1889–94. Scholar
  38. 38.
    Halefoglu AM. Magnetic resonance cholangiopancreatography: a useful tool in the evaluation of pancreatic and biliary disorders. World J Gastroenterol. 2007;13:2529–34.CrossRefGoogle Scholar
  39. 39.
    Hekimoglu K, Ustundag Y, Dusak A, Erdem Z, Karademir B, Aydemir S, et al. MRCP vs. ERCP in the evaluation of biliary pathologies: review of current literature. J Dig Dis. 2008;9:162–9.CrossRefGoogle Scholar
  40. 40.
    Hyodo T, Kumano S, Kushihata F, Okada M, Hirata M, Tsuda T, et al. CT and MR cholangiography: advantages and pitfalls in perioperative evaluation of biliary tree. Br J Radiol. 2012;85:887–96. Scholar
  41. 41.
    Banks KP, Song WS. Role of positron emission tomography-computed tomography in gastrointestinal malignancies. Radiol Clin N Am. 2013;51:799–831. Scholar
  42. 42.
    Sacks A, Peller PJ, Surasi DS, Chatburn L, Mercier G, Subramaniam RM. Value of PET/CT in the management of primary hepatobiliary tumors, part 2. Am J Roentgenol. 2011;197:W260–5. Scholar
  43. 43.
    Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, et al. Prognostic factors after surgical resection for intrahepatic, hilar, and distal cholangiocarcinoma. Ann Surg Oncol. 2011;18:651–8. Scholar
  44. 44.
    Ercolani G, Dazzi A, Giovinazzo F, Ruzzenente A, Bassi C, Guglielmi A, et al. Intrahepatic, peri-hilar and distal cholangiocarcinoma: three different locations of the same tumor or three different tumors? Eur J Surg Oncol. 2015;41:1162–9. Scholar
  45. 45.
    Blechacz B. Cholangiocarcinoma: current knowledge and new developments. Gut Liver. 2017;11:13–26. Scholar
  46. 46.
    Ghouri YA, Mian I, Blechacz B. Cancer review: cholangiocarcinoma. J Carcinog. 2015;14:1. Scholar
  47. 47.
    DeOliveira ML. Liver transplantation for cholangiocarcinoma: current best practice. Curr Opin Organ Transplant. 2014;19:245–52. Scholar
  48. 48.
    Sapisochín G, Fernández de Sevilla E, Echeverri J, Charco R. Liver transplantation for cholangiocarcinoma: current status and new insights. World J Hepatol. 2015;7:2396–403. Scholar
  49. 49.
    Levy MF, Somasundar PS, Jennings LW, Jung GJ, Molmenti EP, Fasola CG, et al. The elderly liver transplant recipient: a call for caution. Ann Surg. 2001;233:107–13.CrossRefGoogle Scholar
  50. 50.
    Goere D, Wagholikar GD, Pessaux P, Carrère N, Sibert A, Vilgrain V. Utility of staging laparoscopy in subsets of biliary cancers: laparoscopy is a powerful diagnostic tool in patients with intrahepatic and gallbladder carcinoma. Surg Endosc. 2006;20:721–5. Scholar
  51. 51.
    Ribero D, Pinna AD, Guglielmi A, Ponti A, Nuzzo G, Giulini SM. Surgical approach for long-term survival of patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis of 434 patients. Arch Surg. 2012;147:1107–13. Scholar
  52. 52.
    Poultsides GA, Zhu AX, Choti MA, Pawlik TM. Intrahepatic cholangiocarcinoma. Surg Clin North Am. 2010;90:817–37. Scholar
  53. 53.
    Choi SB, Kim KS, Choi JY, Park SW, Choi JS, Lee WJ, et al. The prognosis and survival outcome of intrahepatic cholangiocarcinoma following surgical resection: association of lymph node metastasis and lymph node dissection with survival. Ann Surg Oncol. 2009;16:3048–56. Scholar
  54. 54.
    De Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29:3140–5. Scholar
  55. 55.
    Vitale A, Spolverato G, Bagante F, Gani F, Popescu I, Marques HP. A multi-institutional analysis of elderly patients undergoing a liver resection for intrahepatic cholangiocarcinoma. J Surg Oncol. 2016;113:420–6. Scholar
  56. 56.
    Cholankeril G, Sahai T, Ahmad A, Somasundar P. Intrahepatic cholangiocarcinoma: improved survival in the elderly with surgical intervention. Abstracts of the 12th World Congress of the International Hepato-Pancreato-Biliary Association, 20-23 April 2016, São Paulo, Brazil. J Hepatobiliary Pancreat Sci. 2016;18(Suppl 1):e1–e384.Google Scholar
  57. 57.
    Nuzzo G, Giuliante F, Ardito F, Giovannini I, Aldrighetti L, Belli G, et al. Improvement in perioperative and long-term outcome after surgical treatment of hilar cholangiocarcinoma: results of an Italian multicenter analysis of 440 patients. Arch Surg. 2012;147:26–34. Scholar
  58. 58.
    Hartog H, Ijzermans JN, van Gulik TM, Koerkamp BG. Resection of perihilar cholangiocarcinoma. Surg Clin North Am. 2016;96:247–67. Scholar
  59. 59.
    Belghiti J, Clavien P, Gadzijev E, Garden JO, Lau W, Makuuchi M. The Brisbane 2000 terminology of liver anatomy and resections. HPB. 2000;2:333–9.CrossRefGoogle Scholar
  60. 60.
    Wiggers JK, Groot Koerkamp B, Cieslak KP, Doussot A, van Klaveren D, Allen PJ, et al. Postoperative mortality after liver resection for perihilar cholangiocarcinoma: development of a risk score and importance of biliary drainage of the future liver remnant. J Am Coll Surg. 2016;223:321–31. Scholar
  61. 61.
    Moole H, Bechtold M, Puli SR. Efficacy of preoperative biliary drainage in malignant obstructive jaundice: a meta-analysis and systematic review. World J Surg Oncol. 2016;14:182. Scholar
  62. 62.
    Miyazaki M, Yoshitomi H, Miyakawa S, Uesaka K, Unno M, Endo I, et al. Clinical practice guidelines for the management of biliary tract cancers 2015: the 2nd English edition. J Hepatobiliary Pancreat Sci. 2015;22:249–73. Scholar
  63. 63.
    Abdalla EK, Barnett CC, Doherty D, Curley SA, Vauthey JN. Extended hepatectomy in patients with hepatobiliary malignancies with and without preoperative portal vein embolization. Arch Surg. 2002;137:675–80.CrossRefGoogle Scholar
  64. 64.
    Glantzounis GK, Tokidis E, Basourakos SP, Ntzani EE, Lianos GD, Pentheroudakis G. The role of portal vein embolization in the surgical management of primary hepatobiliary cancers. A systematic review. Eur J Surg Oncol. 2017;43:32–41. Scholar
  65. 65.
    Wang ST, Shen SL, Peng BG, Hua YP, Chen B, Kuang M. Combined vascular resection and analysis of prognostic factors for hilar cholangiocarcinoma. Hepatobiliary Pancreat Dis Int. 2015;14:626–32.CrossRefGoogle Scholar
  66. 66.
    Neuhaus P, Thelen A, Jonas S, Puhl G, Denecke T, Veltzke-Schlieker W. Oncological superiority of hilar en bloc resection for the treatment of hilar cholangiocarcinoma. Ann Surg Oncol. 2012;19:1602–8. Scholar
  67. 67.
    Kambakamba P, Linecker M, Slankamenac K, DeOliveira ML. Am J Surg. 2015;210:694–701. Scholar
  68. 68.
    Lee W, Han HS, Yoon YS, Cho JY, Choi Y, Shin HK, et al. Laparoscopic resection of hilar cholangiocarcinoma. Ann Surg Treat Res. 2015;89:228–32. Scholar
  69. 69.
    Xu Y, Wang H, Ji W, Tang M, Li H, Leng J, et al. Robotic radical resection for hilar cholangiocarcinoma: perioperative and long-term outcomes of an initial series. Surg Endosc. 2016;30:3060–70. Scholar
  70. 70.
    Takahashi Y, Ebata T, Yokoyama Y, Igami T, Sugawara G, Nagino M. Surgical treatment of perihilar cholangiocarcinoma in octogenarians: a single center experience. J Hepatobiliary Pancreat Sci. 2013;20:324–31. Scholar
  71. 71.
    Akamatsu N, Sugawara Y, Hashimoto D. Surgical strategy for bile duct cancer: advances and current limitations. World J Clin Oncol. 2011;2:94–107. Scholar
  72. 72.
    Bergquist JR, Shubert CR, Ubl DS, Thiels CA, Kendrick ML, Truty MJ, et al. Risk by indication for pancreaticoduodenectomy in patients 80 years and older: a study from the American College of Surgeons National Surgical Quality Improvement Program. HPB (Oxford). 2016;18:900–7. Scholar
  73. 73.
    Liang DH, Shirkey BA, Rosenberg WR, Martinez S. Clinical outcomes of pancreaticoduodenectomy in octogenarians: a surgeon’s experience from 2007 to 2015. J Gastrointest Oncol. 2016;7:540–6.  10.21037/jgo.2016.03.04.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Gerstenhaber F, Grossman J, Lubezky N, Itzkowitz E, Nachmany I, Sever R, et al. Pancreaticoduodenectomy in elderly adults: is it justified in terms of mortality, long-term morbidity, and quality of life? J Am Geriatr Soc. 2013;61:1351–7. Scholar
  75. 75.
    Alvarez-Sánchez MV, Napoléon B. Review of endoscopic radiofrequency in biliopancreatic tumours with emphasis on clinical benefits, controversies and safety. World J Gastroenterol. 2016;22:8257–70. Scholar
  76. 76.
    Smith I, Kahaleh M. Biliary tumor ablation with photodynamic therapy and radiofrequency ablation. Gastrointest Endosc Clin N Am. 2015;25:793–804. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Marco Filauro
    • 1
  • Giulio Angelini
    • 1
  • Federico Fazio
    • 1
  • Andrea Barberis
    • 1
  1. 1.E.O. Ospedali GallieraGenovaItaly

Personalised recommendations